9/3/2020 Why Novartis Lost the Gleevec War in India | by Rahul Matthan | Writings

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Why Novartis Lost the Gleevec War in India

Rahul Matthan Follow
May 27, 2013 · 7 min read

When the Supreme Court of India disallowed Novartis’ appeal against the rejection of its
patent for its international blockbuster cancer drug, ‘Gleevec’, the news of the order sent
shock waves through the world. Concerns were expressed about the signals this
judgment has sent to the rest of the world. There was a fear that India would be seen to
be a nation that does not support innovation - that no big pharmaceutical company will
risk marketing its drugs in India.

However, the judgment itself is far from anti-innovation. It is a reasoned, intellectual

decision based on the specific facts of this case - which are, as it happens, an unlikely
series of events that are near impossible to replicate.

The Supreme Court was called upon to rule on the decision of the Patent Office rejecting
Novartis’ patent application for its blockbuster cancer drug - Gleevec. One of the key
issues raised before the court was whether in fact the molecule in question meets the
test of inventiveness prescribed under Indian law.

The Test of Inventiveness

The Indian Patent Act has a threefold test to determine whether a particular product is
an invention or not. Any qualifying product (i) must be new, (ii) must be capable of
industrial application and (iii) must come into being as a result of an invention which
either entails technical advance over existing knowledge or has an economic
significance and makes the invention not obvious to a person skilled in the art.

After reviewing a host of facts in considerable detail, the Supreme Court came to the
conclusion that Imatinib Mesylate, is covered by the original patent granted to the base
molecule. Apart from anything else, it was a matter of record that the US Board of Patent
Appeals, in granting a patent for beta crystalline form of Imatinib Mesylate, proceeded

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Imatinib Mesylate in non-crystalline form, for the simple reason that it had always
maintained that Imatinib Mesylate is fully a part of the original patent and does not call
for any separate patent.

Given that there was evidence on record that showed that Imatinib Mesylate was covered
under the original Imatinib patent, there was no way that the Supreme Court could hold
that Imatinib Mesylate was novel and qualified as an invention under the Indian Patent
Act.

Evergreening and the Provisions of Section 3(d)

This left the beta crystal of Imatinib Mesylate, which, since it was not specifically covered
under the original patent, could, arguably, be said to meet the threshold of inventiveness
set out in the statute. However, yet another newly minted provision of the Patent Act
came in the way - the prohibition against evergreening in the new Section 3(d).

Amendments to Section 3(d) had been introduced into the Patent Act at the time when
India acceded to its TRIPs obligations to introduce a product patent regime. It was one of
many amendments of the country’s patent law that lay hidden in the shadow of a far
more significant amendment - the deletion of Section 5 of the Act that introduced a
product patent regime into the country. However, when the Gleevec patent came up for
review, the threshold of efficacy laid out in this section assumed significance.

Under the new Section 3(d), the discovery of a new form of a known substance which
does not result in the enhancement of the known efficacy of that substance was not
entitled to a patent. The question, to be decided in the context of the Gleevec patent, was
whether the beta crystalline form of Imatinib Mesylate enhanced the known efficacy of
the base molecule.

A bare reading of the Indian patent application indicated that all the pharmacological
properties of beta crystalline form of Imatinib Mesylate are equally possessed by Imatinib
in free base form or its salt. How then, could the claimed product have any enhanced
efficacy over the known substance of which it is a new form?

It was pointed out to the court that the Imatinib free base is the active therapeutic
ingredient of the drug. However, in its free base form Imatinib has very little or no
solubility. It is, therefore, not capable of being administered as a drug to human beings
and would, if given in solid dosage form, “sit in the stomach like a brick and would pass
out with no therapeutic effect”. The invention of methanesulfonic acid addition salt of
Imatinib makes the same therapeutic ingredient highly soluble, and therefore eminently
suitable for being administered as a drug to humans.

The question before the court then boiled down to whether the increased solubility of
the therapeutic ingredient was enough to qualify under Section 3(d) as an enhancement
of the known efficacy of the substance.

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court was of the view that the test of enhanced
efficacy in case of chemical substances, especially medicine, should receive a narrow
and strict interpretation. Not all advantageous or beneficial properties could be relevant.
Only those properties that directly relate to efficacy (which in case of medicine is its
therapeutic efficacy) would qualify under this test.

While the court did not go into the details of what would constitute therapeutic efficacy,
it concluded that the effects claimed by Novartis in its patent (i.e., beneficial flow
properties, better thermodynamic stability and lower hygroscopicity), have nothing to
do with therapeutic efficacy and therefore do not meet the threshold set out in Section
3(d).

On both these key grounds the Supreme Court found against Novartis and upheld the
rejection of the patent application.

Why Apply for a Beta Crystal Patent

This brings us to a very important question. Why, knowing full well that India’s patent
laws had a strict threshold of efficacy, did Novartis even apply for a patent in respect of
the beta crystalline form of the drug when it could well have applied for a patent in
respect of Imatinib itself? The answer, lies in the particular time in history that Gleevec
was discovered and how that played out in relation to the evolution of Indian Patent law.

Gleevec was invented by Jurg Zimmerman, a Novartis scientist who invented many
derivatives of N-phenyl-2-pyrimidine-amine including CGP 57148, which was later
named Imatinib by the World Health Organisation and eventually marketed as Gleevec.
In 1993, Zimmerman applied for patents for Imatinib in the US and elsewhere around
the world.

The one country in which Novartis did not apply for a patent was India. At that time,
India still operated under a process patent regime for drugs and pharmaceuticals so,
even had it applied in 1993, Novartis would not have been granted a patent for the
Imatinib molecule.

In 1995, when India acceded to the TRIPs agreement, it introduced a system under
which patents could be placed in a “mailbox” so that they could be opened after the
regime changed to a product patent regime. However, by that time, it was too late for
Novartis to file for a patent on the base molecule. In 1998, when Novartis finally applied
for a product patent it had to do so in respect of the beta crystalline form of Imatinib
Mesylate and not the base molecule.

By the time the Indian Government finally implemented a product patent regime in the
country by deleting Section 5 of the Patents Act, it had, along with other developing
countries, won hard fought concessions to the original text of the TRIPs agreement
further to the Doha round of discussions. That, coupled with the intense parliamentary
debates that accompanied the passage of the amendments to the Patents Act, ensured
that the patent law against which the Gleevec application was going to be tested was one
that had specific provisions to prevent evergreening.
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discover, once the mailbox was opened, that the Indian threshold of efficacy was so high
that its application was bound to be rejected.

While it will be hard to completely isolate the case from associated philosophical
discussions such as the need to balance the patent system with the retail cost of life-
saving pharmaceutical drugs, at the end of the day, Novartis was not denied its Gleevec
patent because India wants to keep the price of drugs down, or because Indian courts do
not support innovation. Novartis was simply at the wrong place at the wrong time.

Implications
Much as the judgment seems to go against Novartis, there is some comfort that big
pharmaceutical companies can take from it. In the first place, while the court did lay
down the need to establish therapeutic efficacy under 3(d), it declined to lay down what
would be the test of such therapeutic efficacy. All that is clear is that, in the view of the
court, the enhanced efficacy claimed by Novartis on the facts of this case do not meet
the requirements of Section 3(d). Since the judgment has limited its scope to the specific
facts of this case, judges in future cases will be able to distinguish themselves on the
basis of facts and avoid having to come to the same conclusions.

However, this much is clear. The provisions of Indian law protecting against
evergreening of patents are valid and will be enforced. Indian courts are unlikely to
grant patents on small incremental enhancements unless it can be demonstrated that
those enhancements have a significant therapeutic effect. And if that is the case, then
Indian patent law will do more to encourage innovation than hinder it.

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